The long term goals of this research are to use our rat injury model of cumulative trauma disorder (CTD) to examine the interaction between multiple risk factors that contribute to the development of CTD and to investigate interventions to prevent and reverse work-related musculoskeletal disorders. In this five-year study, we will address three specific aims: 1) to determine the effects of a voluntary low force task performed at low, medium and high repetition rates on motor behavior and pathophysiological outcomes of forelimb and central nervous system tissues; 2) to determine the effects of a voluntary low repetition task performed at low, medium and high force levels of exertion on motor behavior and pathophysiological outcomes of forelimb and central nervous system tissues; and 3) to determine the effects of voluntary task regimens performed at a range of repetition rate and force level combinations on motor behavior and pathophysiological outcomes of forelimb and central nervous system tissues. The objectives for each specific aim are: A) to determine the extent to which the task regimens causes direct mechanical injury to musculoskeletal, peripheral nerve and surrounding connective tissues; B) to determine the extent to which the task regimens stimulate inflammatory cells and inflammatory processes locally and systemically; C) to determine the extent to which the task regimens result in neuroplasticity in the spinal cord and nucleus cuneatus of the brainstem; and D) to determine the extent to which the task regimens cause motor performance and movement pattern changes and their chronological relationship to the peripheral and central tissue changes. Adult rats (360 experimental and 54 controls) will be trained to grasp and pull a small handle at a pre-defined repetition rate- force level combination including 9 permutations ranging from low (1 reach/45 s), to medium (1 reach/30 s), to high (1 reach/15 s) repetition rates and from low (0.2 N), to medium (0.7 N), to high (1.2 N) force levels for 2 hrs/day, three days/wk for up to 8 weeks. At biweekly endpoints, they will undergo testing for video motion analysis of the forepaw, grip strength, forehead sticker removal, and median nerve conduction velocity. They will then be euthanized for examination of muscular, tendinosynovial, skeletal, and neural tissues both local and proximal to the trained forepaw using haematoxylin and immunohistochemical staining and ELISA techniques. Tract tracing will be used to examine reorganization of sensory afferents from the forelimb to the spinal cord and the dorsal column nuclei. Comparisons will be made between the trained and untrained forelimbs and hindlimb tissues used as internal controls, and between trained forelimbs and those of trained and untrained controls. Changes will be monitored across weeks of task performance as well as with increasing repetition rate-force level exposure. Many questions remain about the interaction of task repetition rate and force level in the development of CTD. A more precise understanding of these effects will help to guide therapeutic strategies for preventive and early care of affected individuals, rehabilitation approaches for subacute and chronic cases, and prevention of chronic disability.